All optical metropolitan quantum key distribution network with post-quantum cryptography authentication.

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

Sending or Not-Sending Twin-Field Quantum Key Distribution with Flawed and Leaky Sources.

Twin-field quantum key distribution (TF-QKD) has attracted considerable attention and developed rapidly due to its ability to surpass the fundamental rate-distance limit of QKD. However, the device imperfections may compromise its practical implementations. The goal of this paper is to make it robust against the state preparation flaws (SPFs) and side channels at the light source. We adopt the sending or not-sending (SNS) TF-QKD protocol to accommodate the SPFs and multiple optical modes in the emitted states. We analyze that the flaws of the phase modulation can be overcome by regarding the deviation of the phase as phase noise and eliminating it with the post-selection of phase. To overcome the side channels, we extend the generalized loss-tolerant (GLT) method to the four-intensity decoy-state SNS protocol. Remarkably, by decomposing of the two-mode single-photon states, the phase error rate can be estimated with only four parameters. The practical security of the SNS protocol with flawed and leaky source can be guaranteed. Our results might constitute a crucial step towards guaranteeing the practical implementation of the SNS protocol.

Integrin ß6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin ß6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of ß6 in PDAC remain largely unknown. In the present study, we investigated the expression of ß6 in PDAC and its potential value as a prognostic factor and therapeutic target. ß6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin ß6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for ß6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin ß6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin ß6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC.

[Application of lymph node labeling with carbon nanoparticles in laparoscopic colorectal cancer surgery].

OBJECTIVE: To investigate the value of lymph node labeled with carbon nanoparticles in laparoscopic colorectal cancer resection. METHODS: The clinical data of 53 patients received laparoscopic radical colorectal surgeries in our department from March 2014 to July 2014 was retrospectively analyzed.Among these patients, carbon nanoparticles were injected into the periphery of the tumor under colonoscopy 1-3 days before the operation (the nanoparticle group) in 26 patients, while 27 patients received operation directly (the control group).The number of cleared lymph nodes, tiny lymph nodes (<5 mm), dyed lymph nodes, and lymph node metastatic rate were compared between the two groups. RESULTS: The two groups had no statistical difference in basic characteristics; 434 and 340 lymph nodes were dissected in the nanoparticle group and control group respectively.The average number of cleared lymph nodes(16.7 ± 3.2) in the nanoparticle group was significantly higher than that of the control group(12.6 ± 2.3) (P<0.001). Besides, both the average number and ratio of cleared tiny lymph nodes in the nanoparticle group were significant higher than those of the control group (P<0.001). Moreover, the rate of less than 12 detected lymph nodes in the nanoparticle group was markedly lower than that of the control group (0 vs 33.3%, P=0.001).There was no statistical difference in lymph node metastatic rate between the two groups (P=0.693). CONCLUSION: Application of lymph node labeled with carbon nanoparticles in laparoscopic colorectal cancer surgery could instruct lymph nodes dissection, improve lymph node detection rate, reduce tumor residual rate, improve the accuracy of pathological staging, and guide the postoperative adjuvant therapy.

SDF-1/CXCR4 axis promotes directional migration of colorectal cancer cells through upregulation of integrin αvß6.

Colorectal cancer (CRC) displays a predilection for metastasis to liver. Although stromal cell-derived factor-1 (SDF-1)/CXCR4 plays an important role in the liver metastasis, the molecular mechanism still remains obscure. We previously reported that integrin αvß6 was implicated in the progression of CRC. However, no data are currently available on the cross talk between CXCR4 and αvß6. In the present study, we first demonstrated the cross talk between CXCR4 and αvß6 and their role in liver metastasis of CRC. We analyzed 159 human CRC samples and found that expression of CXCR4 and αvß6 was significantly associated with liver metastasis, and interestingly expression of αvß6 significantly correlated with expression of CXCR4. Both CXCR4 and αvß6 were highly expressed in metastatic CRC cell lines HT-29 and WiDr, whereas both of them were exiguous in non-metastatic cell line Caco-2. Furthermore, inhibition of αvß6 significantly decreased SDF-1α-induced cell migration in vitro. SDF-1/CXCR4 could upregulate αvß6 expression through phosphorylation of ERK and activation of Ets-1 transcription factor. In conclusion, we demonstrate that SDF-1/CXCR4 induces directional migration and liver metastasis of CRC cells by upregulating αvß6 through ERK/Ets-1 pathway. These data support combined inhibition of CXCR4 and αvß6 to prevent development of liver metastasis of CRC.

Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Serum PCSK9 is positively correlated with disease activity and Th17 cells, while its short-term decline during treatment reflects desirable outcomes in ankylosing spondylitis patients.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) participates in the autoimmune disease pathology by regulating T helper (Th) cell differentiation, NF-κB pathway, toll-like receptor 4, etc. This study intended to investigate the association of serum PCSK9 with disease activity, Th cells, and treatment response in ankylosing spondylitis (AS) patients. METHODS: Eighty-nine active AS patients were enrolled in this multicenter, prospective study. Serum was collected from AS patients at week (W)0, W4, W8, and W12, as well as from 20 osteoarthritis patients and 20 healthy controls after enrollment to detect PCSK9 by ELISA. Based on the ASAS40 response at W12, AS patients were classified as responders and non-responders. RESULTS: PCSK9 was increased in AS patients versus healthy controls (P < 0.001) and osteoarthritis patients (P = 0.006). In AS patients, PCSK9 was positively linked with C-reactive protein (CRP) (P = 0.003) and ASDAS-CRP (P = 0.017), but not with other clinical properties (P > 0.05). Besides, PCSK9 was negatively correlated with interleukin-4 (P = 0.034), positively associated with Th17 cells (P = 0.005) and interleukin-17A (P = 0.014), but did not relate to Th1 cells, interferon-γ, or Th2 cells (all P > 0.05). Additionally, PCSK9 was decreased from W0 to W12 in general AS patients (P < 0.001) and responders (P < 0.001) but remained unchanged in non-responders (P = 0.129). Moreover, PCSK9 was lower at W4 (P = 0.045), W8 (P = 0.008), and W12 (P = 0.004) in responders versus non-responders. Furthermore, the treatment options did not affect the PCSK9 level (P > 0.05). CONCLUSION: Serum PCSK9 is positively associated with disease activity and Th17 cells, while its short-term decline reflects desirable treatment response in AS patients.

PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor-κB pathway in ankylosing spondylitis.

OBJECTIVE: Our previous study reveals that proprotein convertase subtilisin/kexin type 9 (PCSK9) is positively related to inflammatory markers, T helper (Th)-17 cells, and treatment response in ankylosing spondylitis (AS) patients. Subsequently, this study aimed to explore the effect of PCSK9 on Th cell differentiation and its potential molecular mechanism in AS. METHODS: Serum PCSK9 was determined by enzyme-linked immunosorbent assay in 20 AS patients and 20 healthy controls (HCs). Then naïve CD4+ T cells were isolated from AS patients and infected with PCSK9 overexpression or knockdown adenovirus followed by polarization assay. Afterward, PMA (an NF-κB activator) was administrated. RESULTS: PCSK9 was increased in AS patients compared to HCs (p < .001), and it was positively related to Th1 cells (p = .050) and Th17 cells (p = .039) in AS patients. PCSK9 overexpression increased the CD4+ IFN-γ+ cells (p < .05), CD4+ IL-17A+ cells (p < .01), IFN-γ (p < .01), and IL-17A (p < .01), while it exhibited no effect on CD4+ IL-4+ cells or IL-4 (both p > .05); its knockdown displayed the opposite function on them. Moreover, PCSK9 overexpression upregulated the p-NF-κB p65/NF-κB p65 (p < .01), while it had no effect on p-ERK/ERK or p-JNK/JNK (both p > .05); its knockdown decreased p-NF-κB p65/NF-κB p65 (p < .01) and p-JNK/JNK (p < .05). Then, PMA upregulates p-NF-κB p65/NF-κB p65 (p < .001) and increased CD4+ IFN-γ+ cells, CD4+ IL-17A+ cells, IFN-γ, and IL-17A (all p < .01), also it alleviated the effect of PCSK9 knockdown on NF-κB inhibition and Th cell differentiation (all p < .01). CONCLUSION: PCSK9 enhances Th1 and Th17 cell differentiation in an NF-κB-dependent manner in AS, while further validation is necessary.

Association of laboratory parameters and genetic polymorphisms with ischemic stroke in Chinese Han population.

Numerous genetic polymorphisms and clinical laboratory parameters are associated with ischemic stroke (IS). However, the results of such studies have frequently been inconsistent. The aim of the present study was to evaluate associations between clinical laboratory parameters with genetic polymorphisms that influence the risk of IS in a Chinese Han population. Clinical laboratory parameters were measured by an automatic biochemical analyzer. Genotype and allele frequencies of the polymorphisms angiotensin-converting enzyme (ACE) D/I, methylene tetrahydrofolate reductase (MTHFR) C677T and ß-fibrinogen (ß-Fg) A/G, 455/148T/C were characterized by restriction fragment length polymorphism-PCR. Furthermore, the gene polymorphisms plasminogen activator inhibitor (PAI)-1-4G/5G and apolipoprotein E (ApoE) ε2,3,4 were characterized by allele-specific PCR. The associations of genotype and allele frequencies of the six risk genes in different groups with clinical laboratory parameters were analyzed by chi-square tests. The distribution maps of the polymorphisms of the six genes and clinical laboratory parameters were compared between a control group of 336 healthy individuals and 762 patients with IS. Certain laboratory parameters were associated with ACE I/D, ß-Fg-455 A/G and PAI-1 4G/5G. The D allele of ACE I/D was associated with high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). Furthermore, high levels of fasting blood glucose, triglyceride and LDL-C were risk factors for IS. There were significant differences in the genotype frequencies of ACE I/D, ß-Fg-455 A/G and ß-Fg-148 T/C between the IS and the control group. In conclusion, clinical laboratory parameters were associated with the risk of polymorphisms of IS-related genes. The present results support the determination of a range of control values of clinical laboratory parameters for common genotypes in patients with diabetes and hyperlipidemia as a strategy for the early prevention of IS.

Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6-extracellular signal-related kinase signaling pathway.

Norcantharidin has been used as an efficacious anticancer drug in China for many years, but its true mechanism remains poorly understood. Intriguingly, in an in vitro series study of anticancer drugs, we found that norcantharidin can effectively inhibit epithelial tumor cells from expressing integrin alphavbeta6. Our previous studies have confirmed that integrin alphavbeta6 is closely relevant to malignant epithelial cell tumor biology behavior, and it can promote cancer cells to invade and metastasize through a special alphavbeta6-extracellular signal-related kinase (ERK) direct signaling pathway. In this study, we investigated the relationship between the norcantharidin anticancer mechanism and integrin alphavbeta6. After HT-29 colon cancer cells were treated with norcantharidin, cell apoptosis increased remarkably. The expression of alphavbeta6 and the amount of p-ERK decreased substantially; simultaneously, the linkage between alphavbeta6 and ERK was barely detectable. However, the expression of other integrins and the levels of mitogen-activated protein kinase hardly changed. On these grounds, we presumed that norcantharidin induced HT-29 colon cancer cell apoptosis through the alphavbeta6-ERK signaling pathway. This finding elicited a novel strategy for targeting the whole alphavbeta6-ERK signal pathway, rather than simply blocking the combining site of alphavbeta6-ERK in colon cancer treatment.

Curcumin protects the pancreas from acute pancreatitis via the mitogen­activated protein kinase signaling pathway.

Curcumin has been demonstrated to reduce markers of inflammation during acute pancreatitis (AP). However, the underlying mechanisms of the protective effects of curcumin are unknown. In the present study the effects of curcumin in an AP animal model and cell models was examined and the underlying mechanisms were investigated. An AP animal model was established by injection of 5% sodium taurocholate into the biliopancreatic duct of rats, and the cell model was established by treatment with 0.5 nM cerulein with an optimal concentration of lipopolysaccharide in AR42J rat pancreatic cancer cells. Amylase activity and arterial blood gas composition were assessed by automatic biochemical and blood gas analyzers. Pathological alteration of the pancreas was determined by hematoxylin and eosin staining. Interleukin (IL­6), tumor necrosis factor (TNF)­α and C­reactive protein (CRP) levels were measured by ELISA. Cell viability was determined by Cell Counting Kit­8 and protein expression levels were assessed by western blotting. Curcumin reduced the ascites volume after 12 and 24 h, the weight of pancreas after 12, 24 and 36 h of surgery, but also attenuated injury to the pancreas. Serum expression levels of TNF­α and CRP were reduced by curcumin. In addition, curcumin decreased the cell viability, amylase activity and the phosphorylation of p38 in AR42J cells, but did not affect the intracellular levels of IL­6 and TNF­α. Curcumin may lower the severity and inflammatory response via the mitogen­activated protein kinase­signaling pathway, to some extent. However, future studies are required to fully understand the protective effects of curcumin on AP.

Suppression of integrin alphaupsilonbeta6 by RNA interference in colon cancer cells inhibits extracellular matrix degradation through the MAPK pathway.

Integrin alphaupsilonbeta6 plays a very important role in the progression of colon cancer cells and is now defined as a novel, independent prognostic indicator for aggressive colon cancer in humans. Herein, we use the RNA interfering technology to downregulate the expression of alphaupsilonbeta6 in colon cancer cells. Our data demonstrate that plasmid vector based shRNA can effectively down-regulate alphaupsilonbeta6 expression in protein and mRNA levels. Supression of integrin alphaupsilonbeta6 inhibits the phosphorylation and nonphosphorylation level of ERK1/2, the secretion of uPA, pro-MMP-9 and pro-MMP-2 in tumor conditioned medium, and more important, inhibits MAPK-dependent [(3)H] labeled collagen IV degradation via the plasminogen activation cascade. Our study demonstrates in vitro that supression of integrin alphaupsilonbeta6 inhibits extracellular matrix degradation through the MAPK pathway.

[A genetic optimization designing method for microorganism detection genechip probe based on genetic algorithm].

A new automatic selection approach of microorganism specific fragment combination is presented in this paper. Genetic algorithm is used to search optimal solution on the basis of classification ability of SNP combination, which is evaluated by the rough set theory. Other related experimental parameters are also been incorporated. Experimental results show that the method can find the best SNP combination pattern efficiently and accurately, which implies that it is a reliable approach to the genechip probe design.

[Effects of antisense 6 gene on colon cancer cells].

OBJECTIVE: To investigate the effect of antisense integrin beta6 gene on the growth of colon cancer cells. METHODS: Expressing vector of antisense alphavbeta6 was constructed. Human colon cancer cells of the line HT29 were cultured and divided into 3 groups: Group A, remaining wild type; Group B, transfected with antisense integrin beta6 gene; and Group C, transfected with blank vector. RT-PCR was used to detect the integrin beta6 mRNA expression of in the HT29 cells. The integrinbeta6 protein expression on the surface of the cells was detected by immunohistochemistry and flow cytometry. The binding between the cells and fibronectin was examined. (3)H-labeled thymidine (T) was added into the culture fluid of the cells, and then the radiation amount was detected every 6 days so as to determine the capacity to proliferation of the cells in vitro. Thirty female nude mice were divided into 3 groups to be injected subcutaneously with suspension of HT29 cells of Groups A, B, and C as mentioned above. Six weeks later the size of tumors was measured and part of the tumor nodules were resected 5 weeks after the inoculation to undergo pathological examination. RESULTS: Compared with Groups A and C, no corresponding band at 141 bp was found in Group B by RT-PCR. Flow cytometry showed that the expression level of beta6 protein had was (0.30 +/- 0.051, 30%), significantly lower than those of Groups A and C [(0.80 +/- 0.038, 80%) and (0.85 +/- 0.045, 85%), both P < 0.01]. The binding between the HT29 cells and fibronectin of Group B was significantly degraded after the further addition of anti-beta1 and anti-alphav in comparison of Groups A and C (both P < 0.01). The accumulation values of (3)H-labeled T of Group B 2, 4, and 6 days after addition were all significantly lower than those of Groups A and C (all P < 0.01). The tumors in 9 of the 10 mice injected with the HT29 cells of Group B disappeared and the tumor in the only one mice in Group B was only less than 1 mm(3), significantly smaller then those in Groups A and C (15 mm(3) on average, all P < 0.01). CONCLUSION: Antisense beta6 gene significantly inhibits the mRNA and protein expression of the beta6 gene, and then inhibits the growth and proliferation of colon cancer cells, thus proving that integrin beta6 plays an important role in the regulation of colon cancer cells.

The adsorption of NO, NH3, N2 on carbon surface: a density functional theory study.

To explore the adsorption mechanism of NO, NH3, N2 on a carbon surface, and the effect of basic and acidic functional groups, density functional theory was employed to investigate the interactions between these molecules and carbon surfaces. Molecular electrostatic potential, Mulliken population analyses, reduced density gradient, and Mayer bond order analyses were used to clarify the adsorption mechanism. The results indicate that van der Waals interactions are responsible for N2 physisorption, and N2 is the least likely to adsorb on a carbon surface. Modification of carbon materials to decorate basic or acidic functional groups could enhance the NH3 physisorption because of hydrogen bonding or electrostatic interactions, however, NO physisorption on a carbon surface is poor. Zig-zag sites are more reactive than armchair sites when these gas molecules absorb on the edge sites of carbon surface. Graphical abstract NH3, N2, NO adsortion on carbon surface.

MicroRNA-299-3p suppresses proliferation and invasion by targeting VEGFA in human colon carcinoma.

Accumulating evidences have shown that microRNAs (miRNAs) are vital regulators and possess huge capabilities in post-transcriptional control. Although a large number of miRNAs have been identified to be dysregulated in human cancers especially in colon cancer, our understandings of the function of most miRNAs are still largely limited. In this study, we have demonstrated that miR-299-3p plays a critical role in suppressing colon carcinoma progression by targeting Vascular Endothelial Growth Factor A (VEGFA). We observed that miR-299-3p was down-regulated in colon carcinoma tissues and colon cancer cell lines. The level of miR-299-3p was significantly negatively correlated with that of VEGFA mRNA level in colon carcinoma. More importantly, the low level of miR-299-3p predicted poor prognosis of colon cancer patients. Functionally, overexpression of miR-299-3p inhibited the proliferation and invasion of colon carcinoma cells and suppressed the growth of colon cancer xenografts in nude mice. Luciferase reporter assays showed that miR-299-3p could target VEGFA 3' UTR. In addition, up-regulation of miR-299-3p decreased VEGFA expression both in vitro and in vivo, showing that miR-299-3p plays a suppressive effect on VEGFA via post-transcriptional control. However, ectopical expression of VEGFA could abrogate this effect and also abolish miR-299-3p-induced inhibition of cell proliferation and invasion. Taken together, our study provides evidences showing that miR-299-3p functions as a suppressor in colon cancer by targeting VEGFA, suggesting that miR-299-3p might serve as a novel target for colon cancer therapy.

Norcantharidin Suppresses Colon Cancer Cell Epithelial-Mesenchymal Transition by Inhibiting the αvß6-ERK-Ets1 Signaling Pathway.

Norcantharidin (NCTD) is an efficacious anti-cancer drug that has been used in China for many years, but its underlying mechanism of action is still not fully understood. In the present study, we found that NCTD could induce morphological changes in colon cancer cells, causing a transition from a spindle-shaped morphology to a typical round or oval shape, which was indicative of a mesenchymal-epithelial transition (MET) process. Next, we investigated the mechanism by which NCTD induced the MET process. Using a transwell assay, we found that NCTD could suppress the migratory and invasive ability of colon cancer cells in a dose-dependent manner. Moreover, NCTD suppressed the expression of integrin αvß6, MMP-3, and MMP-9 as well as the polymerization of F-actin, further supporting its suppressive effect on migratory and invasive ability. Furthermore, the expression of αvß6, N-cadherin, vimentin and phosphorylated ERK was decreased, while the expression of E-cadherin was up-regulated. We verified that phosphorylated Ets1 was down-regulated substantially after treatment with NCTD. Taken together, our data demonstrated that NCTD could inhibit the EMT process of colon cancer cells by inhibiting the αvß6-ERK-Ets1 signaling pathway. This study revealed part of the mechanism through which NCTD could reverse the EMT process in colon cancer.

Effect of vascular endothelial growth factor-C expression on lymph node metastasis in human cholangiocarcinoma.

The present study aimed to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in human cholangiocarcinoma tissues and its role in metastasis in vitro. A total of 65 biopsy samples of cholangiocarcinoma, plus the FRH-0201 cell line, were investigated. The expression of VEGF-C in the human cholangiocarcinoma specimens was evaluated by immunohistochemistry (IHC). The effect of VEGF-C on tumor cell migration and proliferation was measured by MTT and Transwell assays in the FRH-0201 cell line. According to the IHC results, the biopsies of human cholangiocarcinoma were stained positively for VEGF-C, with a positive rate of 75.4% (49/65). Moreover, VEGF-C was expressed at a higher level in the patients with lymph node metastasis than in those without lymph node metastasis. In vitro, VEGF-C exhibited marked growth stimulation below the concentration of 5 ng/ml and was able to promote cholangiocarcinoma cell migration significantly. These findings suggested that VEGF-C may be a useful factor to predict lymph node metastasis in cholangiocarcinoma tissues and indicates that VEGF-C plays a significant role in proliferation and migration in cholangiocarcinoma cells.

Integrinß6-targeted immunoliposomes mediate tumor-specific drug delivery and enhance therapeutic efficacy in colon carcinoma.

PURPOSE: Adjuvant chemotherapy is one of the significant treatments for colon cancer in clinic. However, it does not achieve the desired therapeutic efficacy, largely due to chemotherapeutic resistance. Integrinß6 (ITGB6) is expressed in malignant colonic epithelia, but not in normal epithelia, and is associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, it is necessary to design therapeutic approaches for efficient and targeted drug delivery into ITGB6-positive cancer cells to improve chemotherapeutic efficacy in colon cancer. EXPERIMENTAL DESIGN: PEGylated liposomes were employed to design ITGB6-targeted immunoliposomes, which have ITGB6 monoclonal antibodies (mAbs) conjugated. We evaluated the ITGB6-targeted immunoliposomes internalization into colon cancer cells and examined 5-fluorouracil (5-FU)-induced cellular apoptosis produced by ITGB6-targeted immunoliposomes+5-FU. In addition, the biodistribution and antitumor efficiency of ITGB6-targeted immunoliposomes were observed in vivo. RESULTS: ITGB6-targeted immunoliposomes enhanced cellular internalization in ITGB6-positive colon cancer cells compared with liposomes. Furthermore, the ITGB6-targeted immunoliposome internalization was dependent on the ITGB6 expression level on cellular surface. ITGB6-targeted immunoliposomes decreased the 5-FU IC50 more than 90% in HT-29 and SW480ß6 cells relative to liposomes. Moreover, when loaded with 5-FU, ITGB6-targeted immunoliposomes produced an approximately 1.5-fold higher 5-FU-induced cellular apoptosis rate than liposomes. In vivo, the therapeutic activity of ITGB6-targeted immunoliposomes+5-FU was significantly superior, resulting in 25% to 35% reduction of tumor weight compared with 5-FU or liposomes+5-FU. CONCLUSIONS: ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy.